Dimethylformamide → HCID 21034896, compound

HRID 1833231Notes

Reaction equation

HRID 1833231 reaction equation
CN(C)[CH:3]=[O:4].P(Cl)(Cl)(Cl)=O.[CH2:11]([O:13][C:14]([N:16]1[CH:25]=[CH:24][C:23]2[C:18](=[CH:19][C:20]([O:30][CH3:31])=[C:21]([O:26][C:27](=[O:29])[CH3:28])[CH:22]=2)[CH:17]1[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([O:39][CH2:40][CH3:41])[CH:34]=1)=[O:15])[CH3:12].C([O-])(=O)C.[K+]>ClCCl.O.C(OCC)(=O)C.CCCCCC>[CH2:11]([O:13][C:14]([N:16]1[CH:25]=[C:24]([CH:3]=[O:4])[C:23]2[C:18](=[CH:19][C:20]([O:30][CH3:31])=[C:21]([O:26][C:27](=[O:29])[CH3:28])[CH:22]=2)[CH:17]1[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([O:39][CH2:40][CH3:41])[CH:34]=1)=[O:15])[CH3:12]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 517044Potassium AcetateHCID 69558031HCID 69558031, compound

Product 1

HCID 21034896HCID 21034896, compoundYield 25.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

To anhydrous N,N-dimethylformamide (3.46 mL, 43.5 mmol) at 0° C. was added phosphorus oxychloride (1.83 mL, 19.2 mmol) dropwise. The mixture was warmed to room temperature and stirred for 30 minutes. The mixture was cooled in an ice-bath, and 6-acetoxy-7-methoxy-1-(3-ethoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester (3.7 mg, 8.70 mmol) in dichloromethane (8 mL) was added dropwise. After addition was complete, the mixture was heated on an oil bath for 4 hrs at 80° C. The mixture was cooled to 0° C. and a solution of potassium acetate (5.26 g, 52.2 mmol) in water (10 mL) was added slowly. The mixture was then heated at 80° C. for 20 minutes. The mixture was cooled, poured into water and diluted with dichloromethane (60 mL). The organic layer was washed water (2×80 mL), saturated aqueous sodium bicarbonate solution (50 mL), saturated aqueous sodium chloride solution (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford a crude oil. Flash chromatography (Merck Silica gel 60, 70–230 mesh, 20% ethyl acetate/hexane) afforded 6-acetoxy-1-(3-ethoxy-benzyl)-4-formyl-7-methoxy-1H-isoquinoline-2-carboxylic acid ethyl ester as a colorless oil (1.0 g, 25% yield).

Workup

  1. temperatureThe mixture was cooled in an ice-bath
  2. additionAfter addition
  3. temperaturethe mixture was heated on an oil bath for 4 hrs at 80° C
  4. temperatureThe mixture was cooled to 0° C.
  5. temperatureThe mixture was then heated at 80° C. for 20 minutes
  6. temperatureThe mixture was cooled
  7. washThe organic layer was washed water (2×80 mL), saturated aqueous sodium bicarbonate solution (50 mL), saturated aqueous sodium chloride solution (50 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto afford a crude oil

Sources & evidence

ORD record
ord-cf3df021e01d44b3bc758c909f6e1052
Source dataset
uspto-grants-2006_06
Patent number
US07067529B2

Reaction notes

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